Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Authors:
Susan J Ramus Antonis C Antoniou Karoline B Kuchenbaecker Penny Soucy Jonathan Beesley Xiaoqing Chen Lesley McGuffog Olga M Sinilnikova Sue Healey Daniel Barrowdale Andrew Lee Mads Thomassen Anne-Marie Gerdes Torben A Kruse Uffe Birk Jensen Anne-Bine Skytte Maria A Caligo Annelie Liljegren Annika Lindblom Håkan Olsson Ulf Kristoffersson Marie Stenmark-Askmalm Beatrice Melin Susan M Domchek Katherine L Nathanson Timothy R Rebbeck Anna Jakubowska Jan Lubinski Katarzyna Jaworska Katarzyna Durda Elżbieta Złowocka Jacek Gronwald Tomasz Huzarski Tomasz Byrski Cezary Cybulski Aleksandra Toloczko-Grabarek Ana Osorio Javier Benitez Mercedes Duran Maria-Isabel Tejada Ute Hamann Matti Rookus Flora E van Leeuwen Cora M Aalfs Hanne E J Meijers-Heijboer Christi J van Asperen K E P van Roozendaal Nicoline Hoogerbrugge J Margriet Collée Mieke Kriege Rob B van der Luijt Susan Peock Debra Frost Steve D Ellis Radka Platte Elena Fineberg D Gareth Evans Fiona Lalloo Chris Jacobs Ros Eeles Julian Adlard Rosemarie Davidson Diana Eccles Trevor Cole Jackie Cook Joan Paterson Fiona Douglas Carole Brewer Shirley Hodgson Patrick J Morrison Lisa Walker Mary E Porteous M John Kennedy Harsh Pathak Andrew K Godwin Dominique Stoppa-Lyonnet Virginie Caux-Moncoutier Antoine de Pauw Marion Gauthier-Villars Sylvie Mazoyer Mélanie Léoné Alain Calender Christine Lasset Valérie Bonadona Agnès Hardouin Pascaline Berthet Yves-Jean Bignon Nancy Uhrhammer Laurence Faivre Catherine Loustalot Saundra Buys Mary Daly Alex Miron Mary Beth Terry Wendy K Chung Esther M John Melissa Southey David Goldgar Christian F Singer Muy-Kheng Tea Georg Pfeiler Anneliese Fink-Retter Thomas v O Hansen Bent Ejlertsen Oskar Th Johannsson Kenneth Offit Tomas Kirchhoff Mia M Gaudet Joseph Vijai Mark Robson Marion Piedmonte Kelly-Anne Phillips Linda Van Le James S Hoffman Amanda Ewart Toland Marco Montagna Silvia Tognazzo Evgeny Imyanitov Claudine Issacs Ramunas Janavicius Conxi Lazaro Iganacio Blanco Eva Tornero Matilde Navarro Kirsten B Moysich Beth Y Karlan Jenny Gross Edith Olah Tibor Vaszko Soo-Hwang Teo Patricia A Ganz Mary S Beattie Cecelia M Dorfling Elizabeth J van Rensburg Orland Diez Ava Kwong Rita K Schmutzler Barbara Wappenschmidt Christoph Engel Alfons Meindl Nina Ditsch Norbert Arnold Simone Heidemann Dieter Niederacher Sabine Preisler-Adams Dorotehea Gadzicki Raymonda Varon-Mateeva Helmut Deissler Andrea Gehrig Christian Sutter Karin Kast Britta Fiebig Dieter Schäfer Trinidad Caldes Miguel de la Hoya Heli Nevanlinna Kristiina Aittomäki Marie Plante Amanda B Spurdle Susan L Neuhausen Yuan Chun Ding Xianshu Wang Noralane Lindor Zachary Fredericksen V Shane Pankratz Paolo Peterlongo Siranoush Manoukian Bernard Peissel Daniela Zaffaroni Bernardo Bonanni Loris Bernard Riccardo Dolcetti Laura Papi Laura Ottini Paolo Radice Mark H Greene Phuong L Mai Irene L Andrulis Gord Glendon Hilmi Ozcelik Paul D P Pharoah Simon A Gayther Jacques Simard Douglas F Easton Fergus J Couch Georgia Chenevix-Trench

Hum Mutat 2012 Apr 14;33(4):690-702. Epub 2012 Feb 14.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, California, USA.

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

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http://dx.doi.org/10.1002/humu.22025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458423PMC
April 2012
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References

(Supplied by CrossRef)
Common alleles at 6q25
Antoniou et al.
1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum Mol Genet 2011
Evaluation of association methods for analysing modifiers of disease risk in carriers of high-risk mutations
Barnes et al.
Genet Epidemiol

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